The pursuit of new composite materials is driven in part by the need for materials which exhibit combined selected properties of the constituent components making up the composite. A very useful class of inorganic materials is the ceramics, examples being metal oxides and metal phosphates or any other inorganic (ceramic or glass) material characterized by ionic and/or covalent interatomic bonding and typically displaying brittle fracture with stresses exceeding the fracture strength.
Typically, ceramics are able to resist compressive forces very well but not tensile or shear forces. This limits the usefulness of ceramics for many load-bearing applications as well as methods for forming to final shape thus presenting a major drawback for using this material for many applications for which the ceramic would otherwise be very suitable or desirable. However, many ceramics can provide high stiffness to structures by virtue of their high elastic modulus and they can also provide good wear resistance. Their brittle behaviour is related to the inability to plastically deform resulting in easy crack initiation at surface or internal flaws and defects introduced either during material formation or fabrication of components. Cutting or grinding operations can introduce micro-cracks within ceramic parts that can act as additional critical stress concentrators promoting easy unstable crack propagation.
By comparison, polymers are relatively compliant and characterized by a low elastic modulus and the ability to deform significantly prior to failure typical of polymeric materials and so it would be useful to be able to produce a composite material that combines the hardness and high modulus of ceramics with the deformability of polymers thereby creating novel materials with enhanced energy absorption capability and fracture resistance. For example, there are many applications for light-weight energy absorbing structures such as crash resistant barriers, bullet- or explosion-proof protective gear and fracture resistant ceramic-based structural materials. Also, formation of such materials would allow certain machining or shaping procedures that cannot be applied to conventional ceramics because of their intrinsic brittleness and inability to tolerate defects introduced during machining and shaping.
Formation of new ceramic-based materials able to resist easy crack initiation and propagation would potentially provide materials with the benefits of ceramics (hardness, wear resistance, higher stiffness than organic polymers) that could be used reliably in certain load-bearing applications. Such materials would be less susceptible to fracture as a result of unintended mishandling, unexpected loading, or microdamage introduced through machining and forming operations.
Currently, strategies for forming tougher ceramics include introducing crack arrestors (boundaries between different phases or lamellae that can de-bond during crack propagation causing crack deflection), or promoting residual compressive stresses in the materials through selection and combination of materials with appropriate thermal expansion coefficients, or through ‘alloying’ to retain metastable phases that can transform during loading thereby creating zones of residual compression at crack tips (transformation induced toughening), or through substitution of larger ions into the crystal lattice of the ceramic to cause residual compressive stresses. None of these approaches focuses on reducing local stress concentrations that can result in crack initiation by re-distributing stresses through a well-bonded, compliant organic phase.
Combining a porous inorganic ceramic with an appropriate infiltrating polymer to form an interpenetrating phase composite, offers a novel strategy for improving the toughness and strength of ceramic-based composites. The combination of ceramic and organic polymer also makes possible a very low density final composite thereby providing superior specific strength and toughness properties (i.e. strength and toughness per weight).
A particular field using ceramics based on calcium polyphosphates is biomedical or dental applications that require biodegradable structures for implants and the like. Calcium polyphosphates (CPP) are inorganic polymers [Ca(PO3)2]n consisting of networks of oxygen-bridged (PO4)3− tetradedra and shared Ca2+ ions (one per pair of phosphate tetrahedra). Studies by the inventors have shown that porous structures made of CPP are biodegradable and, as such, offer potential for a number of novel biomaterial applications including use as substrates for forming tissue-engineered implants for the repair and augmentation of degraded soft and hard tissues and, in particular, for anchoring soft connective tissues to bone (e.g. cartilage or ligament to bone) [Filiaggi M J et al, Bioceramics 11:341-344, 1998; Pilliar R M et al, Biomaterials 22:963-972, 2001; Grynpas M D et al, Biomaterials, 23:2063-2070, 2002; Waldman S et al, J Biomed Mater Res., 62:323-330, 2002]. Porous CPP substrates of desired structure can be formed by sintering CPP powders of appropriate size.
Cell culture methods can then be used to form tissues such as articular cartilage firmly anchored to the porous CPP (through mechanical interdigitation of the in vitro-formed cartilage with the porous CPP structure). The porous CPP also allows bone ingrowth throughout its open-pored structure following implantation in vivo thereby providing a means for securely anchoring articular cartilage or other soft connective tissues (e.g. ligament, tendon, fibrocartilage) to bone. Articular cartilage-CPP ‘plugs’ so formed potentially represent a novel approach for the repair of focal cartilage defects that, if left untreated, may progressively increase in size leading eventually to the need for total joint replacement surgery using traditional implants made of metals, polymers, or ceramics. It is recognized that this traditional approach has a finite lifetime (approximately 15 years for normally active individuals). The consequences for treatment of younger individuals (those less than 55 years old) is that revision surgery represents an inevitable consequence following primary placement of conventional joint replacement implants as used today assuming patient survival.
Therefore it would be very advantageous to develop an alternative treatment approach involving the use of tissue-engineered implant systems for early-stage replacement of identified focal cartilage defects using porous CPP structures as substrates on which suitable tissues can be grown and anchored in vitro prior to implantation of the tissue-CPP ‘plug’ into an identified defect site. In this manner, the defective region of cartilage and underlying subchondral bone (which may or may not be degraded) is replaced by newly-formed healthy tissues. With time the biodegradable CPP component will degrade, being replaced wholly by bone and the overlying articular cartilage surface layer. The porous CPP construct serves as a temporary template for both in vitro and in vivo tissue formation (e.g. cartilage and bone). Our ongoing animal studies have demonstrated the ability to repair osteochondral defects by this method. The results of these studies using sheep (knee joint defects) have been encouraging in our initial short-term (3 month) experiments. Longer-term studies of in vivo degradation rates of the porous CPP constructs placed in rabbit femoral condyle sites have been reported [Grynpas M D et al, Biomaterials, in press, 2002]. Future studies are planned to investigate the response over the longer-term of osteochondral defect repair ‘plugs’.
A key to the development of these novel biphasic (i.e. CPP+cartilage tissue) ‘plugs’ is the formation of a suitable porous CPP substrate. It is therefore important to develop methods for reliably forming porous CPP structures of desired strength and architecture. It is known that an interconnected porous network with an average pore size in the range of 50 to 100 microns will allow rapid bone ingrowth provided that the materials forming the porous structure are biocompatible and suitable initial stability is maintained during early healing [Pilliar R M, J Biomed Mater Res., 21:1-33, 1987]. It is critical that the porous CPP ‘plugs’ exhibit sufficient strength to allow handling including an ability to be forcefully press-fitted into a prepared site (necessary for achieving the required initial stability) as well as being able to withstand any imposed forces due to normal activities preceding extensive bone ingrowth. Previous studies have indicated that an initial porosity corresponding to about ˜35 volume percent of appropriate pore size range (˜50 to 100 μm) appears suitable for both securely anchoring articular cartilage during its in vitro formation and allowing rapid bone ingrowth in vivo.
Therefore, it is necessary to be able to reproducibly achieve the desired open-pored structure while maintaining reasonable mechanical strength of the porous CPP. Due to the inorganic nature of CPP, this presents a challenge since porous ceramic structures in general have low fracture resistance, particularly under complex loading conditions involving tension and shear. Some of the inventors have previously experienced some success in forming suitable porous CPP constructs and had progressed to the point of demonstrating the feasibility of in vitro tissue formation and anchorage to a porous CPP substrate as proposed. This resulted in a U.S. Provisional patent application that was submitted in May 1998 followed subsequently by a full filing and a U.S. patent being granted in June 2000 as U.S. Pat. No. 6,077,989. However, during the course of these early studies, difficulties were encountered in reproducibly forming components of acceptable strength and structure. Thus, development of a method of processing CPP ceramics including the sintering conditions required to achieve reproducible structures reliably is a necessary condition to develope this alternative treatment approach. Such a method would be very useful in general to processing of any ceramic material that have the requisite properties to be processed in a similar way to CPP.
In addition to being able to reproducibly produce ceramics with desired porosity and connectivity of the pores, as mentioned above, it would be very advantageous to provide a method for increasing the mechanical strength and reducing the brittleness of ceramics. Previous studies in 1998 [Cipera E, MASc Thesis, University of Toronto, 1998] have shown that infusing porous CPP structures with a known biodegradable polymer (polycaprolactone (PCL)) resulted in significant increases in the energy to fracture compared with uninfiltrated porous CPP. However, the properties of the organic phase (polycaprolactone) were not considered ideal both in terms of its degradation rate and its ability to wet the CPP phase. Thus a different approach is required in order to develop novel biodegradable composite structures consisting of interpenetrating inorganic (CPP) and organic polymeric phases, both components being biodegradable at appropriate rates that confer greater mechanical strength to the ceramic phase. Such interpenetrating phase composites (IPC) would be useful for fabricating implants for use in assisting bone fracture repair (e.g. fracture fixation plates, intramedullary rods, screws, pins).